BIMT 17: a putative antidepressant with a fast onset of action?
BIMT 17, the only compound reported to be a full 5-HT1A agonist and a 5-HT2A antagonist at the frontal cortex, was assessed in three animal paradigms sensitive to antidepressants in rats: olfactory bulbectomy (OB), differential-reinforcement-of-low rate 72-s (DRL 72-s) and learned helplessness (LH). In the OB rats, BIMT 17, given once daily for 14 consecutive days at an i.p. dose of 10 mg/kg, but not of 20 mg/kg, reduced the increase in ambulation of OB rats, 24 h after the last administration. In the DRL 72-s test, BIMT 17 had a different profile than imipramine. A single i.p. injection of 5, 10, 15 or 20 mg/kg BIMT 17, in contrast to the same doses of imipramine, did not affect response and reinforcement rate in DRL 72-s 1 h after the administration. On the other hand, BIMT 17 slightly shifted the peak of the interresponse time (IRT) distribution towards shorter IRT duration, while imipramine shifted the peak of the IRT distribution towards longer IRT duration. In the LH test, acute oral doses (36, 48 or 60 mg/kg) of BIMT 17, given 30 min before testing, reduced the number of escape failures in LH without altering the intertrial crossings. This effect was also induced by a repeated, but not single, administration with 8 or 16 mg/kg imipramine. The plasma levels following i.p. 10 or oral 48 mg/kg BIMT 17 were in the same range. These results indicate that BIMT 17 does not behave like imipramine in all the tests, and suggest that BIMT 17 acts through different mechanisms of action than imipramine. Only clinical trials will tell whether these mechanisms will be relevant, but if so, BIMT 17 might induce a faster onset of therapeutic activity.
Borsini
F
F
Boehringer Ingelheim Italia, Milano, Italy.
Cesana
R
R
Kelly
J
J
Leonard
B E
BE
McNamara
M
M
Richards
J
J
Seiden
L
L
D000818:Animals; D000928:Antidepressive Agents / Q000097:blood / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D001562:Benzimidazoles / Q000097:blood / Q000494:pharmacology*; D006380:Helplessness, Learned; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009830:Olfactory Bulb / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule
D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D001562:Benzimidazoles; C098107:flibanserin; D007099:Imipramine